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Background Continuous glucose monitoring (CGM) is becoming the standard device for managing glucose levels in patients with type 2 diabetes mellitus (T2DM), and ambulatory glucose profile (AGP) is recommended for use. However, the relationship between AGP indexes and standardized CGM metrics has not been clarified in large-scale studies. Methods This is an exploratory cross-sectional analysis of baseline data collected from a prospective, multicenter 5-year follow-up observational study conducted and published previously by our group. The study participants were 999 outpatients with T2DM who used CGM at baseline, and had no apparent history of cardiovascular disease. We investigated the relationship between average inter-quartile range (IQR) and time in range (TIR). Results In both the TIR >70% and TIR >90% achievement groups, the average IQR was notably small compared to the non-achievement groups. Particularly in comparison of the TIR quartiles, the average IQR became significantly smaller as the TIR became larger. The average IQR correlated negatively with TIR, and the cutoff values for TIR >70% achievement and TIR >90% achievement were average IQR (70/90) 2.13/1.85 mmol/L. Conclusions Our results showed a negative correlation between TIR and the range of blood glucose variations visually represented in AGP. We also estimated for the first time the cutoff values to achieve the TIR target values. The results also showed that the range of blood glucose variations in AGP is associated with indices of intraday and interday blood glucose variations and also with hypoglycemia. Our results may provide new perspectives in the assessment and application of AGP in the clinical setting. This article is protected by copyright. All rights reserved.

There are no large-scale studies on the association between time in range (TIR) and hemoglobin A1c (HbA1c) in Japanese patients with type 2 diabetes mellitus (T2DM) only. The aim of this study was to define the relationship between TIR and HbA1c levels in Japanese patients with T2DM. The glycemic profile of 999 patients was analyzed with FreeStyle Libre Pro Continuous Glucose Monitoring (FLP-CGM) while they continued their prescribed glucose-lowering medications. FLP-CGM data recorded over 8 consecutive days were analyzed. The regression model for HbA1c on TIR was HbA1c = 9.4966 − 0.0309×TIR. The predicted HbA1c level for TIR of 70% was 7.33%, and is higher than recent reports subjecting mostly T1DM. The TIR corresponding to HbA1c 7.0% was 80.64%. HbA1c level correlated significantly with many FLP-CGM-derived metrics. The patients with low TIR tended to have long history of diabetes, on higher daily insulin dose and had high body mass index, HbA1c, liver dysfunction and triglyceride. Furthermore, relatively higher percentages of patients of this group used sulfonylureas, glinides, glucagon like peptide-1 receptor agonists and insulin. Our data showed that the predicted HbA1c corresponding to TIR is largely depends on the study population, thus is not uniform. Our results provide new insights on the management of T2DM.

Introduction A recent study demonstrated that large glucose fluctuations were associated with an increased incidence of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction. However, it is unknown whether glucose fluctuations are related to the incidence of CVD or the progression of atherosclerosis in patients with T2DM with no apparent history of CVD. In this protocol, we will be investigating the relationships of glucose fluctuations evaluated by continuous glucose monitoring (CGM) to the incidence of composite cardiovascular events and the progression of atherosclerosis in patients with T2DM who had no apparent history of CVD. Methods This is a prospective, multicenter, 5-year follow-up observational study. Between April 2018 and October 2019, 1000 participants are expected to be recruited at 34 medical institutions. CGM using FreeStyle Libre Pro is useful for evaluating glucose fluctuations by continuously monitoring glucose levels in interstitial fluid for up to 14 days. The primary study outcome is the relationship between fluctuations in glucose levels evaluated by CGM and the incidence of composite cardiovascular events. Secondary outcomes include the relationships of fluctuations in glucose levels evaluated by CGM to changes in carotid intima media thickness evaluated by echography or grayscale median (an index of tissue characteristics of the carotid wall), brachial–ankle pulse wave velocity, development or progression of diabetic retinopathy or nephropathy, quality-of-life-related diabetes therapy, quality of sleep, development of dementia, and autonomic nerve function. Planned Outcome This protocol is designed to investigate the relationship between glucose fluctuations and the incidence of composite cardiovascular events. We completed the registration of 1000 participants in March 2019. Thus, results will be available in 2024. We expect that evaluating glucose fluctuations will aid the identification of patients with a high probability of developing CVD. Trial Registration ClinicalTrials.gov identifier, UMIN000032325. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-0665-8) contains supplementary material, which is available to authorized users.

Background The association between glucose variability and the progression of atherosclerosis is not completely understood. We aimed to evaluate the associations of glucose variability with the progression of atherosclerosis in the early stages. Methods We conducted a cross-sectional analysis to investigate the associations of glucose variability, assessed by continuous glucose monitoring, with intima-media thickness (IMT) and gray-scale median (GSM) of the carotid arteries, which are different indicators for the progression of atherosclerosis. We used baseline data from a hospital-based multicenter prospective observational cohort study among Japanese patients with type 2 diabetes without a history of cardiovascular diseases aged between 30 and 80 years. Continuous glucose monitoring was performed by Freestyle Libre Pro, and glucose levels obtained every 15 min for a maximum of eight days were used to calculate the metrics of glucose variability. IMT and GSM were evaluated by ultrasonography, and the former indicates thickening of intima-media complex in the carotid artery wall, while the latter indicates tissue characteristics. Results Among 600 study participants (age: 64.9 ± 9.2 (mean ± SD) years; 63.2%: men; HbA1c: 7.0 ± 0.8%), participants with a larger intra- and inter-day glucose variability had a lower GSM and most of these associations were statistically significant. No trend based on glucose variability was shown regarding IMT. Standard deviation of glucose (regression coefficient, β = − 5.822; 95% CI − 8.875 to − 2.768, P P = 0.002), mean amplitude of glycemic excursion (β = − 1.689; − 2.567 to − 0.811, P P P = 0.002) had a statistically significant association with mean-GSM after adjustment for conventional cardiovascular risk factors, including HbA1c. No metrics of glucose variability had a statistically significant association with IMT. Conclusions Continuous glucose monitoring-assessed glucose variability was associated with the tissue characteristics of the carotid artery wall in type 2 diabetes patients without cardiovascular diseases.

Background Previous studies have suggested that high mean glucose levels and glycemic abnormalities such as glucose fluctuation and hypoglycemia accelerate the progression of atherosclerosis in patients with type 2 diabetes. Although continuous glucose monitoring (CGM) that could evaluate such glycemic abnormalities has been rapidly adopted, the associations between CGM-derived metrics and arterial stiffness are not entirely clear. Methods This exploratory cross-sectional study used baseline data from an ongoing prospective, multicenter, observational study with 5 years of follow-up. Study participants included 445 outpatients with type 2 diabetes and no history of apparent cardiovascular disease who underwent CGM and brachial-ankle pulse wave velocity (baPWV) measurement at baseline. Associations between CGM-derived metrics and baPWV were analyzed using multivariate regression models. Results In a linear regression model, all CGM-derived metrics were significantly associated with baPWV, but HbA1c was not. Some CGM-derived metrics related to intra-day glucose variability, hyperglycemia, and hypoglycemia remained significantly associated with baPWV after adjusting for possible atherosclerotic risk factors, including HbA1c. Based on baPWV ≥ 1800 cm/s as indicative of high arterial stiffness, multivariate logistic regression found that some CGM-derived metrics related to intra-day glucose variability and hyperglycemia are significantly associated with high arterial stiffness even after adjusting for possible atherosclerotic risk factors, including HbA1c. Conclusions Multiple CGM-derived metrics are significantly associated with baPWV and high arterial stiffness in patients with type 2 diabetes who have no history of apparent cardiovascular disease. These metrics might be useful for identifying patients at high risk of developing cardiovascular disease.

The aim of this study was to define the relationship between time in range (TIR) and hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM).The glycemic profile of 999 Japanese patients was analyzed with FreeStyle Libre Pro Continuous Glucose Monitoring (FLP-CGM) while they continued their prescribed glucose-lowering medications. FLP-CGM data recorded over 8 consecutive days were analyzed.The regression model for HbA1c on TIR was HbA1c = 9.4966-0.0309 × TIR. The predicted HbA1c level for TIR of 70% was 7.33% and is higher than reports subjecting mostly T1DM. The TIR corresponding to HbA1c 7.0% was 80.64%. The patients with low TIR tended to have long duration of diabetes, used high dose of daily insulin, high body mass index, high HbA1c, liver dysfunction and high triglyceride. Relatively higher percentages of patients of this group used sulfonylureas, glucagon like peptide-1 receptor agonists and insulin.Our data showed predicted HbA1c corresponding to TIR is largely depends on study population, thus is not uniform. Our results provide new insights on the management of T2DM. However, caution should be exercised in extending the HbA1C-TIR relationship using FLP-CGM to any other sensors since there could be a risk of hypoglycemia in doing so.

Background Previous studies have suggested that high mean glucose levels and various glycemic abnormalities such as glucose fluctuation and hypoglycemia accelerate the progression of atherosclerosis in patients with type 2 diabetes. Although continuous glucose monitoring (CGM) that could evaluate such glycemic abnormalities has been rapidly adopted, the associations between CGM-derived metrics and arterial stiffness are not entirely clear. Methods This is an exploratory analysis of an ongoing prospective, multicenter, 5-year follow-up observational study. Study participants included 445 outpatients with type 2 diabetes who underwent CGM and brachial-ankle pulse wave velocity (baPWV) measurement at baseline. Associations between CGM-derived metrics and baPWV were investigated using multivariate regression models.Results In a linear regression model, all CGM–derived metrics were significantly associated with baPWV, but HbA1c was not. Some CGM–derived metrics related to intra-day glucose variability, hyperglycemia, and hypoglycemia remained significantly associated with baPWV after adjusting for possible atherosclerotic risk factors, including HbA1c. Based on baPWV ≥1,800 cm/s as indicative of high arterial stiffness, multivariate logistic regression found that some CGM-derived metrics related to intra-day glucose variability and hyperglycemia are significantly associated with high arterial stiffness even after adjusting for possible atherosclerotic risk factors, including HbA1c.Conclusions Multiple CGM-derived metrics are significantly associated with baPWV and high arterial stiffness in patients with type 2 diabetes who have no history of apparent cardiovascular disease. These metrics might be useful for identifying patients at high risk of developing cardiovascular disease.This study has been registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000032325).

IntroductionPreventing the development and progression of diabetic microvascular complications through optimal blood glucose control remains an important challenge. Whether metrics based on continuous glucose monitoring are useful for the management of diabetic microvascular complications is not entirely clear.Research design and methodsThis is an exploratory analysis of an ongoing prospective, multicenter, 5-year follow-up observational study. Study participants included 999 outpatients with type 2 diabetes who underwent continuous glucose monitoring at baseline. Associations between continuous glucose monitoring-derived metrics and the severity of diabetic retinopathy or albuminuria were investigated using multivariable proportional odds models.ResultsThe overall prevalence of diabetic retinopathy was 22.2%. Multivariate analysis with proportional odds models demonstrated that continuous glucose monitoring-derived metrics related to intraday and interday glucose variability are significantly associated with the severity of diabetic retinopathy, even after adjusting for various possible risk factors. However, significant relationships were not observed after adjusting for hemoglobin A1c (HbA1c) levels. The prevalence of microalbuminuria and macroalbuminuria was 20.3% and 6.7%, respectively. Similarly, multivariate analysis demonstrated that those metrics are significantly associated with the severity of albuminuria. These relationships remained significant even after further adjusting for HbA1c levels.ConclusionsContinuous glucose monitoring-derived metrics related to intraday and interday glucose variability are significantly associated with the severity of diabetic retinopathy or albuminuria in patients with type 2 diabetes. Thus, evaluating these metrics might possibly be useful for risk assessment of diabetic microvascular complications.Trial registration number UMIN000032325.

The aim of the present study was to determine the extent to which respondents provided the same answers to a health-related lifestyle questionnaire in self- and interviewer-administered forms. A total of 234 subjects completed a 110-item questionnaire in both interviewer and self-administered forms. Modes of administration were separated by a 2-week interval. The order was determined by random allocation. The presence and the extent of the tendency to give socially acceptable responses were evaluated using percentage of bias calculated as the ratio of the difference in proportion of positive responses or the mean between interviews and questionnaires and those in questionnaires. All percentages of bias were in the positive direction, ranging from 1.4% (physical exercise) to 26.1% (general life stress). The average percentage of bias was higher in women than in men and were stronger for younger respondents. The age differences between interviewer and respondent were inversely and most strongly related to percentage of bias. Self- and interviewer-administered questionnaires yield very similar results in discriminating between subjects, but the interviewer-administered questionnaire showed systematically more desirable responses to questions related to lifestyle factors. The differences in characteristics between interviewer and respondent may be important determinants of the socially desirability bias in the interview.